ABSTRACT Support is requested for a Keystone Symposia conference entitled Organs- and Tissues-on-Chips, organized by Drs. Christopher P. Austin, Danilo Tagle, Christine L. Mummery and Brian R. Berridge. The conference will be held April 8-12, 2018 at Big Sky Resort, Big Sky, Montana USA. More than 30% of promising medications have failed in human clinical trials because they are found to be toxic despite promising pre-clinical studies in two dimensional cell culture and animal models. Another 60% fail due to lack of efficacy. Consequently, although several thousand diseases affect the human population, only about 500 have approved treatments. However, due to the growing understanding of human biology along with increased availability of innovative technologies, there is now an unprecedented opportunity to translate scientific discoveries more efficiently into new, more effective and safer health interventions. Organs- or Tissues-on-Chips are innovative, alternative approaches that would enable early indications and potentially more reliable readouts of toxicity and efficacy. These microfabricated devices recapitulate the multicellular architectures, tissue-tissue interfaces, physicochemical microenvironments, vascular perfusion and innervation, producing in essence microphysiological systems that mimic human tissue and organ functionality in ways that cannot be recapitulated with conventional culture systems. Through innovative biosensing and readout approaches, these devices employ high-resolution, real-time imaging and non-invasive analysis of biochemical, genetic and metabolic activities of living cells in a functional tissue and organ context. This technology has great potential to advance the study of tissue development, organ physiology and disease etiology. In the context of drug discovery and development, it should be especially valuable for the study of molecular mechanisms of action, prioritization of lead candidates, toxicity testing and biomarker identification. These microfabricated devices have also proven to be useful for modeling human diseases. This conference will touch on ongoing efforts and various applications of tissue-on-chips technology to studies in precision medicine, environmental exposures, reproduction and development, cancer and for use at the International Space Station.